Search PubMed⌕ Search

Biomedical subjects

M Laule

Publications and source records attributed to M Laule.

31 records · Page 2Linked to original sources
PubMed1999

Phase-related changes in right ventricular cardiac output under volume-controlled mechanical ventilation with positive end-expiratory pressure.

OBJECTIVE: To examine determinants of right ventricular function throughout the ventilatory cycle under volume-controlled mechanical ventilation with various positive end-expiratory pressure (PEEP) stages. DESIGN: Prospective observational animal pilot study. SETTING: Animal research laboratory at a university hospital. SUBJECTS: Eight healthy swine under volume- controlled mechanical ventilation. INTERVENTIONS: Flow probes were implanted in eight swine in order to continuously measure blood flow in the pulmonary artery and inferior vena cava. After a recovery phase of 14 days, the swine were subjected to various PEEP stages (0, 5, 10 cm H2O) during volume-controlled positive pressure ventilation. MEASUREMENTS AND MAIN RESULTS: Continuous flow measurement took place in the pulmonary artery and inferior vena cava. Data on standard hemodynamic parameters were additionally acquired. Respiration-phase-specific analysis of right ventricular cardiac output and of additional hemodynamic function parameters followed, after calculation of mean values throughout five respiration cycles. PEEP at 5 cm H2O led to significant decreases in inferior vena cava flow (4.1%), and in right ventricular cardiac output (5.2%); the respective decreases at PEEP 10 cm H2O were 13.9% and 18.3%. In the inspiration phase at PEEP 10 cm H2O, results revealed an overproportionally pronounced decrease in comparison with the expiration phase in inferior vena cava flow (-24.6% vs. -10%) and right ventricular cardiac output (-35% vs. -13.5%). This phenomenon is presumably caused by a PEEP-related increase in mean airway pressure by the amount of 10.7 cm H2O in inspiration. CONCLUSIONS: Increases in PEEP during volume-controlled mechanical ventilation leads to respiration-phase-specific reduction of right ventricular cardiac output, with a significantly pronounced decrease during the inspiration phase. This decrease in cardiac output should be taken into particular consideration for patients with already critically reduced cardiac output.

Airway Resistance↗
PubMed1999

Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with coronary artery disease.

Oxidative damage is a major cause of atherosclerosis. Since human paraoxonase has been postulated as a factor which plays a role in protection from low density lipoprotein oxidation, recent studies have dealt with the impact of hereditary PON1 gene polymorphisms as risk factors for coronary artery disease (CAD). The results from these studies are conflicting. In a case-control study, 1000 Caucasian patients with angiographically confirmed CAD were recruited and matched by age and gender to 1000 control individuals. PON1 mutations in codons 55 and 192 were evaluated by polymerase chain reaction-restriction fragment length polymorphism and allocated to defined haplotypes *1 (55L/192Q), *2 (55L/192R), and *3 (55M/192Q). Frequency of PON1 genotypes without any mutation (PON1*1/*1, wild-type) in CAD cases was 16.9% versus 17.1% in control individuals. PON1*2/*2 showed a frequency of 6.6% versus 7.3% (P = 0.68 compared to wild-type), and PON1*3/3 occurred in 11.8% in CAD cases versus 10.3% among control individuals (P = 0.40). There was also no difference in the distribution of carriers heterozygous for *2 or *3 among cases and control individuals. A haplotype containing both mutations 55M and 192R was not observed. None of the investigated genotypes demonstrated association with early manifestation, severity of disease, acute coronary syndromes, or myocardial infarction. Logistic regression analysis with adjustment for age, gender, diabetes, hypertension, hypercholesterolemia and smoking revealed no evidence of increased coronary risk associated with PON1 genotypes. These results suggest that PON1 polymorphisms are not major genetic determinants of CAD.

Alleles↗
PubMed1998

Arrhythmogenic effects induced by coronary conversion of pulmonary big endothelin to endothelin: aggravation of this phenomenon in heritable hyperlipidemia.

OBJECTIVES: We investigated whether endogenous pulmonary big endothelin has arrhythmogenic properties under normal conditions and in heritable hyperlipidemia. BACKGROUND: Endothelin (ET), one of the most potent vasoconstrictors, is known to induce ventricular arrhythmias. It is unclear, however, whether its precursor, big endothelin, released from the lung, contributes to arrhythmogenesis. METHODS: In a lung-heart model in which a Langendorff heart is serially perfused with the effluent from the isolated lung of the same animal, we evaluated arrhythmias in control and in Watanabe heritable hyperlipidemic (WHHL) rabbits. RESULTS: In both controls (n=12) and WHHL (n=8), serial perfusion evoked a decrease in coronary flow (controls, -11+/-3%; WHHL, -25+/-6%) and a fourfold increase of ventricular extrasystoles (VES) (controls, 40.7+/-8; WHHL, 40.2+/-5 VES/40 min, p < 0.05). However, WHHL developed more and longer nonsustained ventricular tachycardias (VT) compared with controls (incidence, 1.38+/-1.1 vs. 0.33+/-0.5 VT/40 min, p < 0.05; length, 14.36+/-3.1 vs. 7.25+/-1.5 beats/VT, p < 0.05). Arrhythmias were not ischemia-induced because corresponding mechanical flow reduction had no arrhythmogenic effect (n=6 in controls and WHHL). Although vasoconstriction disappeared entirely, arrhythmias were only partly suppressed by ET(A) antagonists (BQ-123, 2 micromol/liter; A-127722, 20 micromol/liter). The ET-converting enzyme inhibitor phosphoramidon (50 micromol/liter) completely suppressed arrhythmias and vasoconstriction. The ET(B) antagonists (IRL-1038, 4 micromol/liter; IRL-1025, 5 micromol/liter) had no effect (n=6). CONCLUSIONS: Endogenous pulmonary big ET produces arrhythmogenic effects that are aggravated in heritable hyperlipidemia. These effects, requiring coronary conversion of big ET into ET, are partly ET(A)-mediated and ET(B)-independent.

Animals↗
PubMed1998

Fibrinogen breakdown, long-lasting systemic fibrinolysis, and procoagulant activation during alteplase double-bolus regimen in acute myocardial infarction.

Recent clinical studies comparing accelerated versus bolus administration of alteplase tissue plasminogen activator (t-PA) suggest similar thrombolytic efficacy, but reveal higher bleeding complications among older patients during the double-bolus regimen. The objective of the present study was to characterize the hemostatic profile of t-PA administered as double-bolus doses of 50 mg, at intervals of 30 minutes. Among 50 patients with acute myocardial infarction treated by double-bolus t-PA thrombolysis, coagulation and fibrinolysis parameters, as well as t-PA levels, were monitored. Monitored t-PA levels peaked at 5 and 35 minutes and were detectable within the therapeutic range even after 90 minutes. Marked systemic fibrinolytic activation was indicated by 75% depletion of both plasminogen and fibrinogen, as well as by 19-fold and 300-fold increases of fibrin degradation and fibrinogen degradation products. Plasminogen-activator inhibitor activity was completely suppressed. Pronounced procoagulant activation was reflected by a 3.4-fold increase of both factor XIIa and prothrombin fragment 1+2, and by a threefold increase of thrombin-antithrombin complex. Independent of t-PA weight dosage, fibrinolytic activation was more pronounced among older patients (> or = 63 years). We conclude that t-PA after bolus administration has a long half-life. Double-bolus regimen leads to a long-lasting systemic fibrinolytic state, which is even more remarkable among older patients--a fact that may explain the higher bleeding complications reported for this age group.

Aged↗
PubMed1998

Coronary constriction and consequent cardiodepression in pulmonary embolism are mediated by pulmonary big endothelin and enhanced in early endothelial dysfunction.

OBJECTIVES: Myocardial ischemia plays a central role in the development of right ventricular failure after acute pulmonary embolism. This study investigates whether pulmonary mediators act specifically on coronary tone and cardiac contractile function in acute pulmonary microembolization and whether such effects are altered in the case of early systemic atherosclerosis. We employ a novel model of serial perfusion in which an isolated rabbit heart is perfused with the effluent of the same animal's isolated lung. DESIGN: Controlled experiment using isolated organs. SETTING: Experimental laboratory. SUBJECTS: Male New Zealand White rabbits (controls). Age-matched, male Watanabe rabbits (hypercholesterolemic, development of accelerated atherosclerosis). INTERVENTIONS: Seven isolated control and seven isolated Watanabe hearts were perfused with the saline effluent of the same animal's isolated lung. After the assessment of the baseline data, the lungs were gradually embolized with glass beads measuring 100 microm in diameter to induce an increase in mean pulmonary arterial pressure from 6 to 8 mm Hg, at baseline, up to 25 mm Hg. MEASUREMENTS AND MAIN RESULTS: Pulmonary embolization to 25 mm Hg evoked a coronary constriction, measured as coronary flow decrease to 89 +/- 7% of the baseline value in controls. In the Watanabe group, coronary constriction was significantly enhanced, compared with controls, with coronary flow decreasing to 76 +/- 6% of the baseline value. In both groups, coronary constriction was followed by a deterioration in cardiac contractile performance. This cardiodepression was significantly deeper in Watanabe hearts with respect to both maximum ventricular pressures and maximum rates of pressure development and decline. Coronary constriction and cardiodepression were prevented by coronary infusion of the nonselective endothelin antagonist PD-145065, the endothelinA antagonists A-127722 and BQ-123, and the endothelin-converting enzyme inhibitor phosphoramidon. Concentration of big endothelin in pulmonary effluent increased from 5.6 +/- 0.3 pmol/L in controls and 5.6 +/- 0.2 pmol/L in the Watanabe group, at baseline, to 8.8 +/- 0.4 pmol/L in controls and 8.9 +/- 0.4 pmol/L in the Watanabe group, at 25 mm Hg pulmonary arterial pressure. Endothelin was not detectable at any time during the experiment in pulmonary effluent. The coronary gradient, calculated as a difference in concentration between coronary and pulmonary effluent, was negative for big endothelin and positive for endothelin in both groups. CONCLUSIONS: We have demonstrated that an increase in pulmonary release of big endothelin occurs during lung embolism, which, in turn, results in coronary constriction and consequent cardiodepression. This action of big endothelin is based on its local coronary conversion into endothelin. In addition, coronary endothelial dysfunction, attributed to early systemic atherosclerosis, was shown to represent a specific risk factor in these events.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Pulmonary big endothelin affects coronary tone and leads to enhanced, ET(A)-mediated coronary constriction in early endothelial dysfunction.

BACKGROUND: Lung tissue produces a variety of mediators; however, little is known regarding how these mediators affect coronary regulation and myocardial contractility. In a novel rabbit lung-heart model, we investigated the possible influence exerted by pulmonary mediators on coronary tone both under normal conditions and in early endothelial dysfunction. METHODS AND RESULTS: In our model, the effluent from the isolated lung is used to serially perfuse the coronary vessels of the isolated heart of the same animal. Compared with the hearts of control rabbits, isolated hearts of Watanabe rabbits revealed pharmacological evidence of endothelial dysfunction and a significant steeper decrease of coronary flow during serial perfusion of the coronary vessels with lung effluent (75+/-6% versus 89+/-3%). This decline in coronary flow was prevented by the nonselective endothelin (ET) antagonist PD-145065, the ET(A) antagonists BQ-123 and A-127722, and the endothelin-converting enzyme inhibitor phosphoramidon. The concentration of big ET in lung effluent ranged from 5.5 to 5.8 pmol/L in both control and Watanabe groups, with levels in corresponding coronary effluent falling to 0.9 to 1.1 pmol/L in controls and to 1.0 to 1.2 pmol/L in the Watanabe group. In either group, ET was not detected in lung effluent, but it rose significantly in coronary effluent during serial perfusion. CONCLUSIONS: Pulmonary big ET, locally converted into ET during coronary passage, causes an ET(A)-mediated elevation in coronary tone under basal conditions as well as an enhanced coronary constriction when early endothelial dysfunction is present.

Acetylcholine↗
PubMed1988

Influence of AV synchrony on the plasma levels of atrial natriuretic peptide (ANP) in patients with total AV block.

ANP was determined in 13 patients with DDD pacemakers due to total AV block, at rest and during bicycle ergometry under both pacing modes, DDD and VVI (7O/min). Under DDD pacing, the mean ANP level (normal range 5-95 pg/mL) at rest was 36 +/- 18 pg/mL (mean +/- SD) and increased significantly by the factor of 3.5 to 1 27 pg/mL during exercise (p less than 0.01). By just changing the pacing mode to VVI, the ANP levels rose to 73 +/- 28 pg/mL (p less than O.0 1) at rest (= 203% of DDD resting level) and to 216 +/- 184 pg/mL (= 170% of DDD peak level) during exercise P less than 0.01). These results show that under AV synchronous pacing, the ANP levels we generally lower. A possible explanation for this increased release of ANP during asynchronous VVI pacing is the acute increase of the atrial wall tension which occurs when the atria contacts during the systole against closed AV valves.

Aged↗
PubMed1988

A new multisensor pacing system using stroke volume, respiratory rate, mixed venous oxygen saturation, and temperature, right atrial pressure, right ventricular pressure, and dP/dt.

A new multisensor pacing device using respiratory rate (RR), stroke volume (SV), oxygen saturation (SO2), temperature (T), right atrial pressure (RAP), right ventricular pressure (RVP) and right ventricular dP/dt, has been developed. It consists of a 7F multisensor catheter and an external pacing unit. It allows simultaneous recording of the input signals and the corresponding data can be compared among the different parameters under identical conditions. Furthermore, several parameters can be combined in such a way as to form a new combination better suitable for rate responsive pacing. The response of each parameter to exercise was studied in 12 healthy volunteers (mean age: 28 years). Exercise testing was carried out using a bicycle ergometer, with workloads up to 200 W. The dynamic characteristics, response and sensitivity to changes of workloads of each parameter were analyzed and compared to one another. SO2 proved to be a quick responding parameter (less than 10 sec) with higher sensitivity in the low exercise range (less than 75 W), T, on the other hand, responded slowly (greater than 30 sec) to exercise changes and had the highest sensitivity in the exercise range beyond 75 W. RR displayed a slow response (greater than 30 sec) and an adequate sensitivity was only found in the upper exercise range (greater than 100 W). SV reacted rapidly to workload changes (less than 10 sec) but showed poor sensitivity at all exercise levels. RAP, RVP and dP/dt displayed quick responses and constantly good sensitivity throughout the workload range. Furthermore, respiratory rate was easily derived from the RAP curve. Special algorithms were developed for each parameter so that pacing rate would reproduce sinus rate behavior. We found that SO2 and all pressure parameter imitated sinus rate response quite well. When using parameter combinations, SO2 and T proved to be superior. Five patients (mean age 68 years) with third degree AV-block were stimulated temporarily using this system. Compared to fixed rate stimulation (VVI 70), exercise performance improved, using SO2 as the input parameter for rate response, by 25% to 50%.

Adult↗
PubMed1988

First clinical experience with an oxygen saturation controlled pacemaker in man.

This article describes the characteristics of a new implantable pacemaker controlled by right atrial oxygen saturation and reports the first clinical experience in man. During the observation period over 5 months, there was no evidence of malfunction due to tissue growth. The system's reaction to exercise changes proved to be quick (5 s to 17 s); decay times varied depending on the magnitude of the power previously performed. Under various exercise tests, the rate increase was linear to the stress load. Measurements of cardiac output showed the system's hemodynamic feedback and its potential self-optimization of pacing rate.

Aged↗
PubMed1987

[Stroke volume, central venous oxygen saturation and blood temperature as control parameters of frequency-adapted pacemaker stimulation].

In order to compare various physiological parameters under identical conditions and to evaluate the "optimal" combination of parameters for triggering a pacing system, a multisensor-catheter of 7 F size was developed. By this catheter placed in the right ventricular cavity, sinus rate (SR), mixed venous oxygen saturation (SO2), temperature (T) and stroke volume (SV) were continuously recorded in 7 volunteers. SR, T, SO2 and SV were analysed for their steady state relationships to workload (P) and for their dynamic characteristics during standardized exercise tests. During exercise the delay times of SR, SO2 and SV were less than 10 sec., whereas that of T was markedly longer ranging from 70 sec. at low exercise levels to 30 sec. at high levels (200 Watts). During recovery delay times of SR, SO2 and SV ranged from 5 to 10 sec., that of T ranged from 20 to 30 sec. The relationship of SR to the workload (0-200 W) performed was linear (r = 0.98), that of T was linear above 50 Watts (r = 0.92), that of SO2 followed an exponential function (r = 0.89). Initial changes of SV were independent (r = 0.02) of the extent of workload. The sensitivity (S = dV/dP) was calculated from the relationship of the parameters (V) measured to the level of exercise performed. SO2 was highly sensitive at the lower range of exercise (less than 75 W), T became constantly sensitive above 50 W, below 50 W the sensitivity of T was continuously decreasing. SR was constantly sensitive over the whole range of exercise (0-200 W), the initial change of SV was not sensitive to the extent of workload.

Adult↗
PubMed1986

Rate control with an external SO2 closed loop system.

In 20 volunteers (mean age 35.5 y) and 12 pacemaker patients (mean age 68.7 y), central venous oxygen saturation (SO2) was monitored continuously by means of an optical sensor integrated in an external transvenous pacing lead placed in the right ventricular cavity. From the SO2 signal recorded at rest and during various modalities of exercise, an algorithm for controlling pacing rate of an external pacing system was developed. An open loop system was used in the volunteers, allowing the comparison of the computed pacing rate with the individual intrinsic heart rate. There was an excellent correlation between the two frequencies as far as the dynamic characteristics and the steady state relationship were concerned. In five pacemaker patients who were stimulated via the external lead, a closed loop control of pacing rate was used. In one patient with a DDD pacemaker implanted for third degree AV-block, the rate response of the SO2 driven pacemaker was well in accordance with the rate attained with the implanted atrial triggered system. With both pacing modes, exercise capacity as determined on a symptom limited treadmill test was identical. In four patients (3 AV block III, 1 bradyarrhythmia) an improvement in exercise tolerance up to 65 percent could be demonstrated with the rate responsive pacing mode. In all patients, it could be shown that an autoregulating pacemaker system with SO2 is an open possibility.

Adult↗
PubMedDate not supplied

Hyperhomocysteinaemia and adverse events complicating coronary catheter interventions.

BACKGROUND: Since hyperhomocysteinaemia is an independent risk factor for development of atherosclerosis as well as for arterial and venous thrombosis we investigated whether elevated homocysteine levels are associated with procedural excess risk which complicates coronary interventions including coronary angioplasty (PTCA), stenting, or directional coronary atherectomy (DCA). DESIGN: Consecutive cases receiving coronary catheter interventions. SETTING: Tertiary referral centre in Germany. METHODS: Fasting total plasma homocysteine levels (tHcy) were determined in 648 consecutive coronary artery disease patients who underwent catheter interventions (272 PTCA, 102 DCA, and 274 stenting). Hyperhomocysteinaemia was defined as tHcy >/=15 micromol/l. The patients were investigated for a 30-day composite endpoint, including need for target-vessel revascularization, myocardial infarction, and death. RESULTS: Among the 648 patients, 78 (12%) demonstrated elevated tHcy levels. The composite endpoint occurred in 41 patients (6.3%). For the entire intervention group there was no evidence that hyperhomocysteinaemia was associated with excess procedural risk (odds ratio [OR]: 1.27; 95% confidence interval [CI]=0.52 to -3.13; P=0.62). In further analyses according to device, hyperhomocysteinaemia also failed to predict complications in the device related subgroups. CONCLUSION: The results indicate that hyperhomocysteinaemia is not a major risk factor for 30-day adverse events complicating PTCA, DCA, or stenting.

Aged↗